Garner C E, Matthews H B
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Toxicol Appl Pharmacol. 1998 Apr;149(2):150-8. doi: 10.1006/taap.1998.8370.
The fate of selected mono-, di-, tetra-, and hexachlorobiphenyls was investigated following single dermal administration (0.4 mg/kg) to determine the effects of chlorine substitution on the dermal absorption and disposition of polychlorinated biphenyls (PCBs). Single dermal doses of 14C-labeled mono-, di-, tetra-, and hexachlorobiphenyls were administered to 1-cm2 areas on the backs of F-344 male rats. Unabsorbed radioactivity was removed from the dose site either at euthanasia or 48 h postdose. Distribution of radioactivity in the dose site and selected tissues was determined by serial sacrifice at time points up to 2 weeks. Dermal penetration varied inversely with degree of chlorination and at 48 h ranged from ca. 100% for monochlorobiphenyl to ca. 30% for the hexachlorobiphenyl. Penetration rate constants correlated well with log kow. PCBs were retained in the epidermis for up to 2 weeks postdose. The data from these studies suggest that systemic absorption of PCBs involves a combination of sequential processes including penetration across the stratum corneum, possibly metabolism in the epidermis and/or dermis, adsorption to proteins, and finally absorption into the systemic circulation. The skin favors the rapid absorption of less chlorinated PCBs, but the relatively rapid metabolism and elimination of these compounds would result in lower body burdens. More highly chlorinated PCBs penetrate less rapidly but remain in the site of exposure and slowly enter the systemic circulation. The dermal absorption of a commercial PCB mixture was modeled, and the results suggest that the net result of the differences in absorbance rates would be a greater body burden of higher chlorinated PCBs relative to those that have a lower chlorine content.
在对F-344雄性大鼠背部1平方厘米的区域单次经皮给予(0.4毫克/千克)选定的单氯、二氯、四氯和六氯联苯后,研究了它们的命运,以确定氯取代对多氯联苯(PCBs)经皮吸收和处置的影响。将14C标记的单氯、二氯、四氯和六氯联苯的单次经皮剂量给予大鼠。在安乐死时或给药后48小时,从给药部位去除未吸收的放射性物质。通过在长达2周的时间点进行系列处死来确定给药部位和选定组织中放射性物质的分布。经皮渗透与氯化程度呈反比,在48小时时,单氯联苯的渗透约为100%,六氯联苯约为30%。渗透速率常数与log Kow相关性良好。给药后长达2周,多氯联苯保留在表皮中。这些研究的数据表明,多氯联苯的全身吸收涉及一系列过程的组合,包括穿过角质层的渗透、可能在表皮和/或真皮中的代谢、与蛋白质的吸附,最终吸收进入体循环。皮肤有利于低氯多氯联苯的快速吸收,但这些化合物相对快速的代谢和消除会导致较低的体内负荷。氯含量更高的多氯联苯渗透较慢,但留在暴露部位并缓慢进入体循环。对一种商业多氯联苯混合物的经皮吸收进行了建模,结果表明,吸收率差异的净结果将是相对于氯含量较低的多氯联苯,氯含量较高的多氯联苯会有更高的体内负荷。